Document Report Card

ID: ALA1135971

Journal: J Med Chem

Title: (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-methylcyclopropyl) glycine is a potent and selective metabotropic group 2 receptor agonist with anxiolytic properties.

Authors: Collado I, Pedregal C, Mazón A, Espinosa JF, Blanco-Urgoiti J, Schoepp DD, Wright RA, Johnson BG, Kingston AE.

Abstract: The asymmetric synthesis and biological activity of (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-methylcyclopropyl) glycine 7 and its epimer at the C3' center 6 are described. Compound 7 is a highly potent and selective agonist for group 2 metabotropric glutamate receptors (mGluRs). It is also systemically 4 orders of magnitude more active in the fear-potentiated startle model of anxiety in rats than the rigid constrained bicyclic system LY354740. Therefore, we have shown that high molecular complexity of conformationally constrained bicyclic systems is not a requirement to achieve highly selective and potent group 2 mGluRs agonists.

CiteXplore: 12166935

DOI: 10.1021/jm0110486